Co-Occurrence of TDP-43 Mislocalization with Reduced Activity of an RNA Editing Enzyme, ADAR2, in Aged Mouse Motor Neurons

摘要: TDP-43 pathology in spinal motor neurons is a neuropathological hallmark of sporadic amyotrophic lateral sclerosis (ALS) and has recently been shown to be closely associated with the downregulation an RNA editing enzyme called adenosine deaminase acting on 2 (ADAR2) ALS patients. Because found more frequently brains elderly patients, we investigated age-related changes localization ADAR2 activity mouse neurons. We that was developmentally upregulated, its mRNA expression level progressively decreased cords aged mice. Motor normally exhibit nuclear immunoreactivity, whereas fast fatigable mice demonstrated loss abnormal localization. Importantly, these expressed significant amounts Q/R site-unedited AMPA receptor subunit (GluA2) mRNA. unedited GluA2 as lethality-causing molecular abnormality observed neurons, results suggest decreases play mechanistic role aging serve one risk factors for ALS.